Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study

PLoS One. 2014 Apr 21;9(4):e94217. doi: 10.1371/journal.pone.0094217. eCollection 2014.

Abstract

Background: Unexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue.

Methods: Fatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56).

Results: The full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05-2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. 'Power of attention' improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate.

Conclusion: A single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency. Overall, the results support the hypothesis that iron deficiency can affect women's health, and a normal iron status should be maintained independent of hemoglobin levels.

Trial registration: ClinicalTrials.gov NCT01110356.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognition
  • Dose-Response Relationship, Drug
  • Endpoint Determination
  • Erythrocyte Indices
  • Fatigue / blood
  • Fatigue / drug therapy*
  • Fatigue / physiopathology
  • Female
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / adverse effects
  • Ferric Compounds / therapeutic use*
  • Hemoglobins / metabolism
  • Humans
  • Intention to Treat Analysis
  • Iron Deficiencies*
  • Maltose / administration & dosage
  • Maltose / adverse effects
  • Maltose / analogs & derivatives*
  • Maltose / therapeutic use
  • Placebos
  • Quality of Life
  • Transferrin / metabolism

Substances

  • Ferric Compounds
  • Hemoglobins
  • Placebos
  • Transferrin
  • ferric carboxymaltose
  • Maltose

Associated data

  • ClinicalTrials.gov/NCT01110356

Grant support

Vifor Pharma Ltd. sponsored this study and supported the study design. Funding was provided for a clinical research organization (SGS Life Sciences Services, Switzerland), statistical analysis (ACOMED statistic, Germany) and manuscript preparation (SFL Regulatory Affairs & Scientific Communication, Switzerland). URL of funder: www.viforpharma.com. The funders had no role in the collection and analysis of the data and the decision to publish the manuscript. Employees of the funder were involved in the study design and reviewed the manuscript as coauthors.